Faculty Bibliography

This randomized, double-blind, placebo-controlled, 6-month trial examined the efficacy and safety of once-daily morning-dosed atomoxetine in adult patients with attention-deficit/hyperactivity disorder (ADHD) and the efficacy of atomoxetine in ameliorating symptoms through the evening hours. Patients received once-daily atomoxetine (n = 250) or placebo (n = 251) in the morning for approximately 6 months. The efficacy measures included the Adult ADHD Investigator Symptom Rating Scale (AISRS), Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version, Clinical Global Impressions-ADHD-Severity of Illness, and Adult ADHD Quality of Life Scale. Overall, 94 patients randomized to atomoxetine and 112 patients randomized to placebo completed the study. On the AISRS total score, Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version evening index total score, Clinical Global Impressions-ADHD-Severity of Illness score, and Adult ADHD Quality of Life Scale total score, atomoxetine was statistically superior to placebo at the 10-week and 6-month time points. From the visitwise analysis, the mean (SD) AISRS total scores for atomoxetine decreased from 38.2 (7.5) at baseline to 21.4 (12.3) at the 6-month end point compared with 38.6 (7.0) to 25.8 (13.2) for placebo (P = 0.035). Nausea, dry mouth, fatigue, decreased appetite, urinary hesitation, and erectile dysfunction were the treatment-emergent adverse events reported significantly more often with atomoxetine. Discontinuations due to adverse events were 17.2% and 5.6% for atomoxetine and placebo, respectively (P < 0.001). Once-daily morning-dosed atomoxetine is efficacious for treating ADHD in adults when measured 10 weeks and 6 months after initiating treatment. Atomoxetine demonstrated significant efficacy that continued into the evening. Adverse events were similar to previous trials

BACKGROUND: To evaluate the effect of atomoxetine (ATX) on attention-deficit/hyperactivity disorder (ADHD) and comorbid social anxiety disorder in adults. METHODS: Randomized, double-blind, placebo-controlled, conducted in adults with ADHD and social anxiety disorder. Patients received 40-100 mg ATX (n=224) or placebo (n=218) for 14 weeks following a 2-week placebo lead-in period. Efficacy measures included the Conners' Adult ADHD Rating Scale: Investigator-Rated: Screening Version (CAARS:Inv:SV), Liebowitz Social Anxiety Scale (LSAS), Clinical Global Impression-Overall-Severity (CGI-O-S), State-Trait Anxiety Inventory (STAI), Social Adjustment Scale-Self Report (SAS), and Adult ADHD Quality of Life Scale-29 (AAQoL). Safety and tolerability were also assessed. RESULTS: ATX mean change (-8.7+/-10.0) from baseline (29.6+/-10.4) on CAARS:Inv:SV Total ADHD Symptoms score was significantly greater than placebo mean change (-5.6+/-10.2) from baseline (31.2+/-9.4; P<.001). ATX mean change (-22.9+/-25.3) from baseline (85.3+/-23.6) on LSAS Total score was significant compared to placebo mean change (-14.4+/-20.3) from baseline (82.1+/-21.3; P<.001). The visit-wise analysis revealed greater improvement on the CAARS:Inv:SV Total ADHD Symptoms score and LSAS Total score for ATX at every time point throughout the study (P values </=.012). Mean changes in CGI-O-S, STAI-Trait Anxiety scores, and AAQoL Total score were significantly greater for ATX compared to placebo. Mean change for both groups on STAI-State Anxiety scores was comparable. Improvement on SAS for ATX compared to placebo was not significant. Rates of insomnia, nausea, dry mouth, and dizziness were higher with ATX than with placebo. Discontinuation rates due to treatment-emergent adverse events were similar between groups. CONCLUSIONS: ATX monotherapy effectively improved symptoms of ADHD and comorbid social anxiety disorder in adults and was well tolerated

In the United States, approximately 4.4% of adults have attention-deficit/ hyperactivity disorder (ADHD), and the average worldwide prevalence in adults is about 3.4%. However, in the United States, only about 1 in 10 adults with ADHD is currently treated specifically for ADHD. Adults with ADHD are likely to have adaptive impairments, evidenced by educational difficulties, a history of erratic employment, relationship and marital difficulties, credit or money problems, driving problems, risky sexual behavior, early parenthood, legal difficulties, poor physical health, and substance abuse problems. The DSM-IV-TR criteria for ADHD were developed for diagnosing children and were not intended for use in adults. To identify symptoms appropriate for ADHD criteria in adults, a study compared the following 3 groups: adults referred to a clinic for ADHD who were subsequently diagnosed with ADHD, a control group of adults referred to the same clinic who thought they had ADHD but did not, and a community control group. ADHD was diagnosed by a structured clinical interview using the DSM-IV-TR criteria but excluding age at onset.

Introduction: The objective of this article is to compare primary care physicians' (POPs') experiences with diagnosing and treating adult attention-deficit/hyperactivity disorder (ADHD) versus other mental health disorders. Methods: Four hundred PCPs who have patients with ADHD, bipolar disorder, depression, generalized anxiety disorder (GAD), or obsessive-compulsive disorder completed a public release survey assessing their experiences and attitudes on diagnosing and treating these disorders. Results: Forty-eight percent of PCPs felt uncomfortable diagnosing adult ADHD and 44% reported that there were no clear diagnostic criteria. Seventy-five percent rated the quality and accuracy of existing adult ADHD diagnostic tools as either poor or fair. Seventy-two percent reported that ADHD is easier to diagnose in children than adults. Sixty-five percent reported deferring to specialists to diagnose adult ADHD, compared to 2% for depression and 3% for GAD. Eighty-five percent reported that they would be more comfortable diagnosing and treating adult ADHD if thorough, straightforward screening tools were validated and if there were effective medications that were neither stimulants nor controlled substances. Discussion: While this survey indicated that adult ADHD is generally accepted by PCPs, the results also indicate that PCPs are significantly less likely to diagnose and treat ADHD in adults without deferring to a specialist, when compared to GAD and depression. The recent development of new screening tools for adult ADHD as well as non-stimulant and novel stimulant medications may reduce PCPs' reliance on specialist referrals. Conclusion: This study highlights a potential need for PCPs for increased education and training in adult ADHD. As the study was conducted 6 years ago, follow-up investigations into the current PCP awareness of adult ADHD are indicated.

OBJECTIVE: The aim of this post hoc analysis was to examine whether tachyphylaxis occurs after repeated courses of antidepressant drug therapy. METHOD: 276 patients with major depressive disorder (MDD) were treated with sertraline (150-200 mg daily) for 8 weeks. Patients with persistent MDD after sertraline therapy were randomized to continuation therapy with either sertraline plus atomoxetine (n = 72) or sertraline plus placebo (n = 74) for 8 additional weeks. Logistic regression was used to test the hypothesis that an increase in prior antidepressant drug exposure is associated with a reduced responsiveness to sertraline therapy. RESULTS: The number of prior antidepressant drug exposures was negatively associated with response to initial sertraline therapy (odds ratio = 0.81, p = 0.0035). The odds ratio indicates a 19.9% reduced likelihood of response with each prior antidepressant treatment trial. In contrast, the number of prior antidepressant treatment trials was not associated with response to continuation sertraline plus atomoxetine or sertraline plus placebo therapy. CONCLUSION: This observation supports the hypothesis that tachyphylaxis may develop after repeated antidepressant drug trials

Many adults with attention-deficit/hyperactivity disorder (ADHD) were never diagnosed as children. The impairment caused by untreated ADHD can complicate, or even lead to, other psychiatric conditions. Accurate diagnosis and efficacious treatment of ADHD in adults, which may include pharmacologic and nonpharmacologic interventions, is vital to improve their functioning. When a patient has ADHD and a co-occurring condition, the clinician should usually treat the most impairing condition first

OBJECTIVE: To assess the quality of life (QOL) in adults with attention-deficit/hyperactivity disorder (ADHD) given triple-bead mixed amphetamine salts (MAS), a long-acting amphetamine formulation designed for a duration of action of up to 16 hours. METHOD: 274 adults with ADHD (DSM-IV-TR criteria) were randomly assigned to 7 weeks of double-blind treatment with an optimal dose of triple-bead MAS (12.5 mg to 75 mg) (N = 137) or placebo (N = 137). As a secondary objective of this study, QOL was assessed on the basis of self-reported Adult ADHD Impact Module (AIM-A) scores, describing ADHD-specific QOL in 6 domains and global QOL (questions 1-4). To assess safety, data were collected on adverse events, vital signs, electrocardiograms, laboratory tests, and sleep quality. The trial was conducted from January 2005 to June 2005. RESULTS: Statistically significant improvement between triple-bead MAS and placebo was observed in all 6 ADHD-specific AIM-A subscales. In addition, statistically significant improvement in global QOL between triple-bead MAS and placebo was seen, based on AIM-A question 1 (p = .0006) and question 4 (p = .0001). Patients' age, gender, race, and prior use of stimulant medication were not found to significantly affect AIM-A subscale scores. The most common treatment-emergent adverse events with triple-bead MAS (insomnia, dry mouth, decreased appetite, headache, and weight decreased) were consistent with amphetamine treatment, and their incidence generally decreased with time. CONCLUSIONS: Adults with ADHD showed significantly improved QOL for both ADHD-specific and global measures with triple-bead MAS in comparison to placebo, based on AIM-A scores. Treatment-emergent adverse events were mostly mild to moderate in intensity and were consistent with amphetamine treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00150579

OBJECTIVE: Previously, data from 97 weeks of open-label atomoxetine treatment of adults with attention-deficit/hyperactivity disorder (ADHD) were reported. This final report of that study presents results from over 4 years of treatment. METHOD: Results were derived from the study of 384 patients (125 patients remaining in the open-label trial since the interim report), receiving up to 221 weeks of treatment. Primary efficacy measure was the Conners' Adult ADHD Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) Total ADHD Symptom score. Adverse events and vital signs were assessed. RESULTS: CAARS-Inv:SV Total ADHD Symptom scores decreased 30.2% (p < .001) during treatment. Similar, significant decreases were noted for the secondary efficacy measures, including the Sheehan Disability Scale Total score, which improved 25.3% (p < .001). Adverse events consisted primarily of pharmacologically (noradrenergic) expected effects. CONCLUSIONS: Results of this open-label study support the long-term efficacy, safety, and tolerability of atomoxetine for the treatment of adult ADHD